Beneficial effects of octreotide in alcohol-induced neuropathic pain. Role of H 2S, BDNF, TNF-α and Nrf2.

Rongqiang Jiang,Hongxia Wei

doi:10.1590/acb360408

Abstract

ABSTRACTPurposeTo explore the role and molecular mechanisms of neuroprotective effects of octreotide in alcohol-induced neuropathic pain.MethodsMale Wistar rats were employed and were administered a chronic ethanol diet containing 5% v/v alcohol for 28 days. The development of neuropathic pain was assessed using von Frey hair (mechanical allodynia), pinprick (mechanical hyperalgesia) and cold acetone drop tests (cold allodynia). The antinociceptive effects of octreotide (20 and 40 µg·kg–1) were assessed by its administration for 28 days in ethanol-treated rats. ANA-12 (0.25 and 0.50 mg·kg–1), brain-derived neurotrophic factor (BDNF) receptor blocker, was coadministered with octreotide. The sciatic nerve was isolated to assess the biochemical changes including hydrogen sulfide (H2S), cystathionine β synthase (CBS), cystathionine γ lyase (CSE), tumor necrosis factor-α (TNF-α), BDNF and nuclear factor erythroid 2-related factor 2 (Nrf2).ResultsOctreotide significantly attenuated chronic ethanol-induced neuropathic pain and it also restored the levels of H2S, CBS, CSE, BDNF, Nrf2 and decreased TNF-α levels. ANA-12 abolished the effects of octreotide on pain, TNF-α, BDNF, Nrf2 without any significant effects on H2S, CBS, CSE.ConclusionsOctreotide may attenuate the behavioral manifestations of alcoholic neuropathic pain, which may be due to an increase in H2S, CBS, CSE, BDNF, Nrf2 and a decrease in neuroinflammation.

Highlights

Alcohol is one of the most commonly abused substances in the world and the development of neuropathic pain is one of the most common serious complications of its chronic consumption[1]
Administration of ethanolic diet (5% v/v) for 28 days led to a significant decrease in paw withdrawal threshold in von Frey hair test, suggesting the development of mechanical allodynia (Fig. 1), increase in paw withdrawal duration in acetone spray test, suggesting the development of cold allodynia (Fig. 2), increase in paw withdrawal duration in the pinprick test, suggesting the development of mechanical hyperalgesia (Fig. 3)
Administration of alcohol for 28 days led to significant development of neuropathic pain assessed in terms of mechanical allodynia, cold allodynia and mechanical hyperalgesia

Summary

Introduction

Alcohol is one of the most commonly abused substances in the world and the development of neuropathic pain is one of the most common serious complications of its chronic consumption[1]. Chronic alcohol consumption induces neuropathological changes[2], which may have diverse manifestations, including the development of pain symptoms in the form of peripheral neuropathy[3]. There is no reliable pharmacological agent for its management and, there is a need to explore new effective agents to ameliorate the symptoms of neuropathic pain. The role of somatostatin receptors, localized on the peripheral primary afferent terminals, in the development of pain sensitization has been reported . Its role and molecular mechanisms in alcoholic neuropathy are not explored yet

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Results

Conclusion